Journal Information
Vol. 36. Issue. 6.November - December 2016
Pages 583-722
Vol. 36. Issue. 6.November - December 2016
Pages 583-722
Letter to the Editor
Open Access
Subacute interstitial pneumonitis due to Mycobacterium bovis after intravesical bacillus Calmette-Guérin instillation in a renal transplant patient
Neumonitis intersticial subaguda por Mycobacterium bovis tras instilaciones vesicales de bacilo de Calmette-Guérin en un trasplante renal
Fernando Caravaca-Fontána,
Corresponding author

Corresponding author.
, Marta Cano Megíasb, Matilde Sánchez-Condec, Sandra Elías Triviñoa, Ana Fernández-Rodrígueza, Fernando Liañoa
a Servicio de Nefrología, Hospital Universitario Ramón y Cajal, Madrid, Spain
b Servicio de Nefrología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares (Madrid), Spain
c Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Article information
Full Text
Download PDF
Full Text
Dear Editor,

The estimated incidence rate of urothelial bladder carcinoma is 1.4–2.2% in kidney transplant (KT) patients.1 However, the clinical course may be more aggressive than in the general population, with higher rates of progression and relapse.2

Intravesical administration of bacillus Calmette-Guérin (BCG), an attenuated live strain of Mycobacterium bovis, is one of the main adjuvant therapies for managing non-invasive bladder cancer. BCG instillation produces a massive local immune reaction with antitumour activity.3 However, both local and systemic infectious complications have been reported in relation to this treatment, especially in immunocompromised patients. Disseminated infection as a result of the systemic absorption of BCG may occur in 0.4% of cases and it is usually manifested as fever, weight loss, night sweats or dyspnoea, and even multiple organ failure in severe cases.4,5 Interstitial pulmonary involvement is a rare complication.

We report for the first time a case of interstitial pneumonitis caused by M. bovis after bladder instillations of BCG in a KT patient.

This case involves an 81-year-old woman with a history of chronic kidney disease secondary to polycystic kidney disease, who underwent kidney transplantation 11 years earlier with a normally functioning graft, in maintenance therapy with tacrolimus and everolimus. Ten years after transplantation, she was diagnosed with urothelial bladder carcinoma without muscle invasion and, after transurethral resection of the tumour, she began treatment with intravesical BCG.

Thirty days after the first instillation she began suffering from asthenia, weight loss, sweating and fever mainly at night, and cough without expectoration, which lasted for 2 months. After receiving 2 cycles of empirical antibiotic therapy with amoxicillin–clavulanic acid and levofloxacin without improvement, the patient returned to the emergency department.

On admission she had a temperature of 38°C and 98% oxygen saturation, with no other noticeable findings. The results of laboratory tests and viral serologies revealed only anaemia of chronic disease and elevated C-reactive protein. Broad-spectrum antibiotic therapy with meropenem was initiated, fever and symptoms persisted during the following days.

All bacterial and viral microbiological studies were negative. A CT scan of the chest, abdomen and pelvis was performed, which showed a lung pattern with diffuse bilateral involvement and poorly defined nodules with a centrilobular distribution, suggestive of infection caused by atypical microorganisms or mycobacteria. The study was completed with a bronchoscopy for microbiological sampling, although direct microscopy showed no acid-alcohol resistant bacilli and cultures of mycobacteria obtained from bronchoalveolar lavage were negative at 8 weeks. The study using the polymerase chain reaction technique for Mycobacterium tuberculosis complex sequences in the bronchoalveolar lavage was also negative. No transbronchial biopsy was performed because it was considered a high-risk procedure for the patient.

With the diagnostic suspicion of systemic lung infection caused by M. bovis, treatment with isoniazid, rifampicin and ethambutol was prescribed for 6 months. Fever and associated symptoms gradually disappeared, while acute-phase reactants decreased. A subsequent control CT scan showed that the impairments described had been resolved.

This clinical case demonstrates the risk of developing systemic complications in KT patients treated with bladder instillations of BCG.

The pathophysiology of pulmonary manifestations after intravesical BCG treatment is still controversial. Some authors believe it is a hypersensitivity reaction, based on the histological finding of granulomas without microbiological isolation and a favourable response to corticosteroids.6 Other authors, however, have reported mycobacterial isolation in different tissues,7 which would demonstrate a haematogenous dissemination of the bacillus. It has therefore been pointed out that the low sensitivity of microbiological studies would be a result of the rapid control of bacillary replication by the host immune system and the attenuated virulence of BCG, which, however, would not prevent the formation of granulomatous lesions.8 Therefore, the diagnosis is made by the presence compatible clinical symptoms and the early response to tuberculostatic treatment.

Some authors argue that intravesical instillation of BCG is safe in immunocompromised patients, however there are no conclusive studies in KT patients.1,4,9 To that effect, concomitant prophylactic administration of isoniazid alone or in combination with rifampicin has been tested, with favourable results in some cases, although not without adverse effects.1 On the other hand, other authors argue that it should be contraindicated due to an increased risk of systemic dissemination together with a lower local immune response.10

In conclusion, bladder instillations of BCG in kidney transplantation can produce disseminated mycobacterial infection, with a long-term clinical course with few symptoms. Therefore, a high index of suspicion is necessary to begin treatment at an early stage.

Conflicts of interest

The authors declare no conflicts of interest related to the publication of this article.

J. Palou, O. Angerri, J. Segarra, J. Caparrós, L. Guirado, J.M. Diaz, et al.
Intravesical bacillus Calmette-Guèrin for the treatment of superficial bladder cancer in renal transplant patients.
Transplantation, 76 (2003), pp. 1514-1516
P.U. Ardelt, M. Rieken, J. Ebbing, G. Bonkat, T. Vlajnic, L. Bubendorf, et al.
Urothelial cancer in renal transplant recipients: incidence, risk factors and oncological outcome.
Urology, 88 (2016), pp. 101-110
A. Böhle, S. Brandau.
Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer.
D.L. Lamm.
Efficacy and safety of bacille Calmette-Guérin immunotherapy in superficial bladder cancer.
Clin Infect Dis, 31 (2000), pp. S86
C.H. Choi, S.O. Lee, G. Smith.
Subclinical miliary Mycobacterium bovis following BCG immunotherapy for transitional cell carcinoma of the bladder.
BMJ Case Rep, 2014 (2014),
M.A. Pérez-Jacoiste Asín, M. Fernández-Ruiz, F. López-Medrano, C. Lumbreras, A. Tejido, R. San Juan, et al.
Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature.
Medicine (Baltimore), 93 (2014), pp. 236-254
L. Eichel, E. Erturk, A. Disant’Agnese.
Drug resistant Mycobacterium bovis cystitis following intravesical bacillus Calmette-Guerin treatment.
J Urol, 162 (1999), pp. 2096
J.D. Colmenero, R. Sanjuan-Jimenez, B. Ramos, P. Morata.
Miliary pulmonary tuberculosis following intravesical BCG therapy: case report and literature review.
Diagn Microbiol Infect Dis, 74 (2012), pp. 70-72
O. Yossepowitch, S.E. Eggener, B.H. Bochner, S.M. Donat, H.W. Herr, G. Dalbagny.
Safety and efficacy of intravesical bacillus Calmette-Guerin. Instillations in steroid treated and immunocompromised patients.
J Urol, 176 (2006), pp. 482-485
M. Babjuk, W. Oosterlinck, R. Sylvester, E. Kaasinen, A. Böhle, J. Palou-Redorta, et al.
EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update.
Eur Urol, 59 (2011), pp. 997-1008

Please cite this article as: Caravaca-Fontán F, Cano Megías M, Sánchez-Conde M, Elías Triviño S, Fernández-Rodríguez A, Liaño F. Neumonitis intersticial subaguda por Mycobacterium bovis tras instilaciones vesicales de bacilo de Calmette-Guérin en un trasplante renal. Nefrologia. 2016;36:711–713.

Copyright © 2016. Sociedad Española de Nefrología
Nefrología (English Edition)

Subscribe to our newsletter

Article options
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?